Biological Effects (Molecular and Cellular)

of Radiation

Compiled by:Prof.Mirza Anwar Baig

Assistant Professor AI's Kalsekar Technical Campus,Navi

Mumabi

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At the end of topic students should be able to

• Describe the biological effects of radiation mentioned in this section.

• Enlist the hazardous effects of the radiations on humans mentioned in the course.

Radiations • Radiation is energy that comes from a source and

travels through some material or through space.

• The different types of radiation differ only in their respective wavelengths

• Low wavelength UV has the highest energy and is potentially the most damaging

• Sunscreens can protect us from UV damage

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The Electromagnetic SpectrumThe Electromagnetic Spectrum

We can see visible light.We can feel the heat from IR and microwave radiation.Our senses cannot detect most of the other wavelengths.

The SunThe Sun’’s Radiations Radiation

• More than half of the sun’s radiation is in the IR region of the spectrum• Nearly 40% is in the visible region of the spectrum• Only 8% is in the UV region, but this higher energy radiation can potential cause damage to living cells

Types of radiations

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Types of Radiation• Radiation is classified into:1. Ionizing radiation (nuclear radiation)

Alpha particlesAlpha particlesBeta particlesBeta particlesGamma rays (or photons)Gamma rays (or photons)X-Rays (or photons)X-Rays (or photons)

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2. 2.Non-ionizing Radiation SourcesNon-ionizing Radiation Sources

Visible lightVisible lightMicrowavesMicrowavesRadiosRadiosVideo Display TerminalsVideo Display TerminalsPower linesPower linesRadiofrequency Diathermy (Physical Radiofrequency Diathermy (Physical Therapy)Therapy)LasersLasers 9

Ionizing Versus Non-ionizing Ionizing Versus Non-ionizing RadiationRadiation

Ionizing RadiationIonizing Radiation–– Higher energy electromagnetic waves Higher energy electromagnetic waves

(gamma) or heavy particles (beta and (gamma) or heavy particles (beta and alpha).alpha).

–– High enough energy to pull electron High enough energy to pull electron from orbit.from orbit.

Non-ionizing RadiationNon-ionizing Radiation–– Lower energy electromagnetic waves.Lower energy electromagnetic waves.–– Not enough energy to pull electron Not enough energy to pull electron

from orbit, but can excite the electron.from orbit, but can excite the electron.10

Factors affecting biological activity of radiations

• Penetrating power of radiations• Tissue sensitivity• Dose (energy) of radiations• Surface area exposed

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Moderately radiosensitive•Skin•Vascular endothelium•Lung•Kidney•Liver•Lens (eye)

Radiosensitivity of tissues

Highly radiosensitive•Lymphoid tissue•Bone marrow •Gastrointestinal epithelium•Gonads•Embryonic tissues

Bone marrowBone marrow SkinSkin CNSCNS

Least radiosensitive•Central nervous system (CNS)•Muscle•Bone and cartilage•Connective tissue

Ionizing (nuclear) radiationA radiation is said to be ionizing when it has enough energy to eject one or more electrons from the atoms or molecules in the irradiated medium.

This is the case of alpha and beta radiations, as well as of electromagnetic radiations such as gamma radiations, X-rays and some ultra-violet rays. Visible or infrared light are not, nor are microwaves or radio waves.

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• Penetration in materials– Outside the body, an alpha emitter is not

a hazard unless it is on the skin– Inside the body, an alpha emitter is a

bigger hazard if it deposits its energy in sensitive tissue

Alpha rays

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• Common alpha-particle emitters– adon-222 gas in the environment– Uranium-234 and -238) in the

environment– Polonium-210 in tobacco

• Common alpha-particle emitter uses– Smoke detectors– Cigarettes/cigars

Sources- Alpha radiations

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• Penetration in materials– At low energies, a beta particle is not very

penetrating – stopped by the outer layer of skin or a piece of paper

– At higher energies, a beta particle may penetrate to the live layer of skin .

– Inside the body, a beta particle is not as hazardous as an alpha particle because it is not as big

– Because it is not as big, it travels farther, interacting with more tissue (but each small piece of tissue gets less energy deposited)

Beta rays

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Gamma radiations• Ionizing power is poor• High penetrating power• Form free radicals• Injurious to health

X raysPenetration power is sufficient to penetrate

tissues and can be detected outside.Ionizing power is low

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Properties of nuclear radiations• High ionizing power- 1. alpha radiations

Moderate ionizing power- beta rad.Low ionizing power- gamma & X rays

High penetrating power- gamma & X raysModerate penetrating power- Beta raysLow penetrating power- alpha rays

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The time scales for the short and long term effects The time scales for the short and long term effects of radiation are symbolized in the figure and listed of radiation are symbolized in the figure and listed

in the tablein the table

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• Radiation Causes Ionizations of:ATOMS

which may affectMOLECULES

which may affectCELLS

which may affectTISSUES

which may affectORGANS

which may affectTHE WHOLE BODY

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Types of UV RadiationTypes of UV Radiation

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Biological Effects of UV RadiationBiological Effects of UV RadiationThe consequences depend primarily on:1. The energy associated with the radiation2. The length of time of the exposure3. The sensitivity of the organism to that

radiation

The most deadly form of skin cancer, melanoma, is linked with the intensity of UV radiation and the latitude at which you live.

Protection from UV RadiationProtection from UV Radiation

Effect of radiation on body(1) Hair

The losing of hair quickly and in clumps occurs with radiation exposure at 200 rems or higher.

(2) BrainSince brain cells do not reproduce, they won't be damaged directly unless the exposure is 5,000 rems or greater. can cause seizures and immediate death.

(3) ThyroidThe thyroid gland is susceptible to radioactive iodine. In sufficient amounts, radioactive iodine can destroy all or part of the thyroid.

(4) Reproductive TractBecause reproductive tract cells divide rapidly, these areas of the body can be damaged at rem levels as low as 200. Long-term, some radiation sickness victims will become sterile.

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(5) Blood SystemWhen a person is exposed to around 100 rems, the blood's lymphocyte cell count will be reduced, victim more susceptible to infection. This refered to as mild radiation sickness. Early symptoms of radiation sickness mimic those of flu.According to data from Hiroshima and Nagaski, show that symptoms may persist for up to 10 years and may also have an increased long-term risk for leukemia and lymphoma.

(6) HeartIntense exposure to radioactive material at 1,000 to 5,000 rems would do immediate damage to small blood vessels and probably cause heart failure and death directly.

(7) Gastrointestinal TractRadiation damage to the intestinal tract lining will cause nausea, bloody vomiting and diarrhea. This is occurs when the victim's exposure is 200 rems or more.

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The Effects of Radiation on the Cell at the Molecular Level

•When radiation interacts with target atoms, energy is deposited, resulting in ionization or excitation.

•The absorption of energy from ionizing radiation produces damage to molecules by direct and indirect actions.

•For direct action, damage occurs as a result of ionization of atoms on key molecules in the biologic system. This causes inactivation or functional alteration of the molecule.

• Indirect action involves the production of reactive free radiacals whose toxic damage on the key molecule results in a biologic effect.

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Damage by ionising radiation

• Indirect effect:– Ionising event can break molecular

bonds but effect may manifest elsewhere

– e.g. ionisation of water molecules can produce free radicals (molecule with unpaired electron in outer shell). •Highly reactive•Capable of diffusing a few micrometres to

reach and damage molecular bonds in DNA 31

Indirect Action• These are effects mediated by free

radicals.• A free radical is an electrically

neutral atom with an unshared electron in the orbital position. The radical is electrophilic and highly reactive. Since the predominant molecule in biological systems is water, it is usually the intermediary of the radical formation and propagation.

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Indirect Action- Radiolysis of Water

Free radicals readily recombine to electronic and orbital neutrality. However, when many exist, as in high radiation fluence, orbital neutrality can be achieved by:

1.Hydrogen radical dimerization (H2)2.The formation of toxic hydrogen peroxide (H2O2).3.The radical can also be transferred to an organic

molecule in the cell.

H-O-H ® H+ + OH- (ionization)H-O-H ® H0+OH0 (free radicals)

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Indirect Action• H0 + OH0 ®HOH (recombination)• H0 + H0 ® H2 (dimer)• OH0 + OH0 ® H2O2 (peroxide dimer)• OH0 + RH ® R0 + HOH (Radical transfer)• The presence of dissolved oxygen can modify

the reaction by enabling the creation of other free radical species with greater stability and lifetimes

• H0+O2 ® HO20 (hydroperoxy free radical)• R0+O2 ®RO20 (organic peroxy free radical)

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Indirect Action - The Lifetimes of Free Radicals

• The lifetimes of simple free radicals (H0 or OH0) are very short, on the order of 10-10 sec. While generally highly reactive they do not exist long enough to migrate from the site of formation to the cell nucleus. However, the oxygen derived species such as hydroperoxy free radical does not readily recombine into neutral forms. These more stable forms have a lifetime long enough to migrate to the nucleus where serious damage can occur.

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Indirect Action- Free Radicals

• The transfer of the free radical to a biologic molecule can be sufficiently damaging to cause bond breakage or inactivation of key functions

• The organic peroxy free radical can transfer the radical form molecule to molecule causing damage at each encounter. Thus a cumulative effect can occur, greater than a single ionization or broken bond.

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BIOCHEMICAL REACTIONS WITH IONIZING RADIATION

• DNA is the most important material making up the chromosomes and serves as the master blueprint for the cell. It determines what types of RNA are produced which, in turn, determine the types of protein that are produced.

I IS-AT-SI IP PI IS-CG-SI IP PI IS-GC-SI IP PI IS-TA-SI I

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• There is considerable evidence suggesting that DNA is the primary target for cell damage from ionizing radiation.

• Toxic effects at low to moderate doses (cell killing, mutagenesis, and malignant transformation) appear to result from damage to cellular DNA. Thus, ionizing radiation is a classical genotoxic agent. 38

• The lethal and mutagenic effects of moderate doses of radiation result primarily from damage to cellular DNA.

• Although radiation can induce a variety of DNA lesions including specific base damage, it has long been assumed that unrejoined DNA double strand breaks are of primary importance in its cytotoxic effects in mammalian cells.

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• Active enzymatic repair processes exist for the repair of both DNA base damage and strand breaks. In many cases breaks in the double-strand DNA can be repaired by the enzymes, DNA polymerase, and DNA ligase.

• The repair of double strand breaks is a complex process involving recombinational events, depending upon the nature of the initial break.

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• Residual unrejoined double strand breaks are lethal to the cell, whereas incorrectly recoined breaks may produce important mutagenic lesions. In many cases, this DNA misrepair apparently leads to DNA deletions and rearrangements. Such large-scale changes in DNA structure are characteristic of most radiation induced mutations.

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Radiation Induced Chromosome Damage

•Chromosomes are composed of deoxyribonucleic acid (DNA), a macromolecule containing genetic information. This large, tightly coiled, double stranded molecule is sensitive to radiation damage. Radiation effects range from complete breaks of the nucleotide chains of DNA, to point mutations which are essentially radiation-induced chemical changes in the nucleotides which may not affect the integrity of the basic structure.

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Radiation Induced Chromosome Damage

•After irradiation, chromosomes may appear to be "sticky" with formation of temporary or permanent interchromosomal bridges preventing normal chromosome separation during mitosis and transcription of genetic information. In addition, radiation can cause structural aberrations with pieces of the chromosomes break and form aberrant shapes. Unequal division of nuclear chromatin material between daughter cells may result in production of nonviable, abnormal nuclei.

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Radiation Induced Membrane Damage• Biological membranes serve as highly specific

mediators between the cell (or its organelles) and the environment. Alterations in the proteins that form part of a membrane ’s structure can cause changes in its permeability to various molecules, i.e., electrolytes. In the case of nerve cells, this would affect their ability to conduct electrical impulses. In the case of lysosomes, the unregulated release of its catabolic enzymes into the cell could be disastrous. Ionizing radiation has been suggested as playing a role in plasma membrane damage, which may be an important factor in cell death (interphase death)

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Cell Cycle• Irradiation of the cell causes cell

death at mitosis as a result of the inability to divide.(Mitotic death)

• RNA and protein synthesis do not halt in the sterilized cell. The result is the production of the giant cell, whose unbalanced growth eventually proves lethal to the cell.

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applications• Contrast media and diagnosis• Therapeutic applications

teletherapy: removal of lesions not possible by surgery (gamma)surface source: dermatologic and ophthalmic use (beta)extracorporeal (on blood vessels): change in immune response (x ray)infusions: to treat peritoneal and pleural diffusion in malignant tumours (gamma and beta ray)

• Diagnostic applications

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